A critical role of placental growth factor in the induction of inflammation and edema formation
| Autor: | Peter Carmeliet, Lawrence F. Brown, Jennifer Bertoncini, Hajimu Oura, Paula Velasco, Michael Detmar |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Vascular Endothelial Growth Factor A
Placental growth factor Angiogenesis medicine.medical_treatment Immunology Neovascularization Physiologic Mice Transgenic Inflammation Endothelial Growth Factors Pregnancy Proteins Biology Biochemistry Capillary Permeability Neovascularization Mice chemistry.chemical_compound Transduction Genetic medicine Animals Edema Humans Hypersensitivity Delayed Placenta Growth Factor Mice Knockout Lymphokines Vascular Endothelial Growth Factors Growth factor Cell Biology Hematology Up-Regulation Vascular endothelial growth factor Vascular endothelial growth factor A chemistry Intercellular Signaling Peptides and Proteins Increased inflammatory response medicine.symptom Megakaryocytes |
| Zdroj: | Blood. 101:560-567 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2002-05-1516 |
| Popis: | Angiogenesis is a prominent feature of a number of inflammatory human diseases, including rheumatoid arthritis, psoriasis, and cutaneous delayed-type hypersensitivity (DTH) reactions. Up-regulation of placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, has been found in several conditions associated with pathologic angiogenesis; however, its distinct role in the control of angiogenesis has remained unclear. To directly investigate the biologic function of PlGF in cutaneous inflammation and angiogenesis, DTH reactions were investigated in the ear skin of wild-type mice, of PlGF-deficient mice, and of transgenic mice with targeted overexpression of human PlGF-2 in epidermal keratinocytes, driven by a keratin 14 promoter expression construct. Chronic transgenic delivery of PlGF-2 to murine epidermis resulted in a significantly increased inflammatory response, associated with more pronounced vascular enlargement, edema, and inflammatory cell infiltration than seen in wild-type mice. Conversely, PlGF deficiency resulted in a diminished and abbreviated inflammatory response, together with a reduction of inflammatory angiogenesis and edema formation. VEGF expression was up-regulated at a comparable level in the inflamed skin of all genotypes. These findings reveal that placental growth factor plays a critical role in the control of cutaneous inflammation, and they suggest inhibition of PlGF bioactivity as a potential new approach for anti-inflammatory therapy. |
| Databáze: | OpenAIRE |
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